February 26, 2020

Snehalata Pawar, Ph.D.

Assistant Professor
Department of Pharmaceutical Sciences
Division of Radiation Health
UAMS College of Pharmacy

Research Interest Statement

My overall research objective is directed toward understanding the molecular mechanisms of radiation-induced normal tissue injury with the goal of developing therapeutic interventions to prevent normal tissue injury, while improving the efficacy of cancer radiotherapy.

Radiation therapy is used to treat a wide variety of cancers. However, despite technological advancements in delivering radiotherapy, normal tissue toxicity to rapidly proliferating cells remains a dose-limiting factor to treat the tumor cells. Further radiation-induced late effects (persistent oxidative stress and inflammation) lead to increased risk of secondary cancers as well as fibrosis, which have a significant impact on the quality of life of cancer survivors.

It is well known that ionizing radiation (IR) injury in cells or organisms elicits signaling mechanisms to modulate increased oxidative stress, apoptosis, DNA damage repair, cell cycle arrest and inflammatory responses. Although C/EBPδ has been implicated in the regulation of targets involved in these biological processes, not much was known about its role in the IR response, when we embarked upon these studies.

We uncovered a novel role for C/EBPδ in promoting post-radiation survival primarily via protection of the intestine and hematopoietic tissues from IR injury. We showed that C/EBPδ modulates IR-induced oxidative stress and mitochondrial dysfunction. Ongoing projects investigate the molecular targets of C/EBPδ that modulate the IR-induced oxidative stress response and mitochondrial dysfunction using a proteomics approach and bioinformatics; the role of C/EBPδ in IR-induced acute injury to hematopoietic stem cells and intestinal stem cells; and the role of toll-like receptor-4 (TLR4) signaling in promoting IR-induced injury to intestine and heart tissues.

Additionally, we are also interested in screening novel drugs/compounds for their potential use as either radiosensitizers of tumor cells or as radioprotectors of normal tissues.

Dr. Pawar’s Cancer-related Grants

US DOD: W81XWH1910737

Snehalata Pawar: Site Project PI

Title “Role of TLR4 in Radiation-induced Cardiomyopathy”

09/15/2019 to 09/14/2022

$499,962*

*total cancer-related direct cost

 

Dr. Pawar’s UAMS Collaborators

UAMS College of Pharmacy

Department of Pharmaceutical Sciences

Antino Allen, Ph.D.

Nukhet Aykin-Burns, Ph.D.

Marjan Boerma, Ph.D.

Brendan Frett, Ph.D.

Martin Hauer-Jensen, Ph.D.

Rupak Pathak, Ph.D.

 

UAMS College of Medicine

Department of Biochemistry and Molecular Biology

Stephanie Byrum, Ph.D.

Alan Tackett, Ph.D.

Dr. Pawar’s External Collaborators

Amrita Cheema, Ph.D., Georgetown University
Eric Pietras, Ph.D., University of Colorado Anschutz Medical Campus
Dirk Pleimes, M.D., Myelo Therapeutics GmbH

Opportunities for Collaboration

I am open to collaborations with basic science colleagues as well as clinicians with interests in myelodysplasia, intestinal inflammatory disorders and researchers interested in improving the efficacy of chemo/radio resistant cancers.

You May Not Know That …

I love gardening, hiking and occasionally volunteering at my son’s school.

Recent Cancer-Related Publications

Pawar SA, Roy-Sarkar T, Kuppuswamy B, Wang J, Zhang Y, Dowdy S, Huang A, Sharan S and Sterneck E. C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression. Proceedings of the National Academy of Sciences, USA, 107: 9210-5, 2010.

Roysarkar T, Sharan S, Wang J, Pawar SA, Cantwell CA, Johnson PF, Morrison DK, Wang JM, Sterneck E. Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBPδ expression and contributes to transformation of breast tumor cells. Molecular and Cellular Biology, 32:320-332, 2012.

Geiger H , Pawar SA, Kerschen EJ , Nattamai KJ , Hernandez I, Liang H-P, Fernández JA, Cancelas JA, Ryan MA, Kustikova O, Schambach A, Fu Q, Wang J, Fink LM, Petersen K-U, Zhou, D, Griffin JF, Baum C, Weiler H, Hauer-Jensen M. Pharmacological targeting of the thrombomodulin–protein C pathway mitigates radiation toxicity. Nature Medicine, 18:1123-1129, 2012.

Pathak R, Pawar SA, Gupta P, Fu Q, Berbée M, Garg S, Sridharan V, Wang W, Biju PG, Kragerly K, Boerma M, Ghosh SP, Cheema AK, Hendrickson HP, Aykin-Burns N and Hauer-Jensen M. Characterization of transgenic Gfrp knock-in mice: Implications for BH4 in modulation of radiation response. Antioxidants Redox Signaling, 20:1436-46, 2014.

Pawar SA*, Shao L , Chang J, Wang W, Pathak R, Wang J, Zhu X, Boerma M, Sterneck E, Zhou, D and Hauer-Jensen M. C/EBPδ deficiency sensitizes mice to ionizing radiation-induced hematopoietic and intestinal injury. PLOS One, 9:e94967, 2014.

Banerjee S, Aykin-Burns N, Krager KJ, Shah SK, Melnyk SB, Hauer-Jensen M, Pawar SA*. Loss of C/EBPδ enhances IR-induced cell death by promoting oxidative stress and mitochondrial dysfunction. Free Radical Biology and Medicine, 99:296-307, 2016.

Banerjee S, Shah, SK, Melnyk SB, Pathak R, Hauer-Jensen and Pawar SA*. C/EBPδ is essential for gamma tocotrienol-mediated protection against radiation-induced hematopoietic and intestinal injury. Antioxidants, 7: 55, 2018.

Banerjee S, Tyler A, Majumdar D, Groves T, Wang J, Gorantla A, Allen AR* and Pawar SA*. Loss of C/EBPδ exacerbates radiation-induced neurocognitive decline by suppression of oxidative stress in aged mice. Int. J. Mol. Sci. 20: 885, 2019.

Garg S, Sadhukhan R, Banerjee S, Savenka AL, Basnakian AG, McHargue V, Wang J, Pawar SA, Ghosh SP, Ware J, Hauer-Jensen M, Pathak R*. Gamma-tocotrienol protects the intestine from radiation potentially by accelerating mesenchymal immune cell recovery. Antioxidants. 8, 57, 2019.

Banerjee S, Fu Q, Melnyk SB, Shah SK, Sterneck E, Hauer-Jensen M, Pawar SA*. C/EBPδ protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress. Sci. Rep., 9:13953, 2019. https://doi.org/10.1038/s41598-019-49437-x

*corresponding author